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Long-Term Hypoxia Alters Endocrine and Physiologic Responses to Umbilical Cord Occlusion in the Ovine Fetus

Hikaru Umezaki, MD

Kanchan M. Kaushal, MIS

Departments of Physiology/Pharmacology and Pediatrics, Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, California

Charles A. Ducsay, PhD

Departments of Physiology/Pharmacology and Pediatrics, Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, California; cducsay{at}som.llu.edu

Objective: This study was designed to determine the effect of umbilical cord occlusion (UCO) on fetal endocrine responses in the long-term hypoxemic (LTH) ovine fetus.

Methods: Pregnant ewes were maintained at high altitude (3820 m) from day 30 of gestation. Normoxic control and LTH fetuses were catheterized, and an inflatable occluder was placed on the umbilical cord at day 132 of gestation. In the LTH group, maternal oxygen tension was maintained at approximately 60 mmHg by nitrogen infusion through a maternal tracheal catheter. On day 137, two 5-minute UCOs were performed. On day 139, the study was repeated with a 10-minute UCO.

Results: Basal adrenocorticotropic hormone (ACTH) levels and peak responses to the first 5-minute UCO were not different between control and LTH fetuses (17.6 ± 4.0 to 418.8 ± 41.3 in controls, 25.7 ± 4.0 to 530.0 ± 93.0 pg/mL in LTH fetuses). A similar pattern was observed during the second UCO. Basal cortisol levels were similar in both groups. In response to UCO, a significant increase in cortisol was observed in both groups, but peak concentrations in the LTH group were significantly higher than those in the control group (23.9 ± 4.8 versus 14.8 ± 2.9 mg/mL, respectively, P < .05). The second occlusion also increased cortisol concentrations, but no differences were observed between groups. After the 10-minute UCO, the ACTH and cortisol responses were similar to the first 5-minute occlusion, with higher cortisol levels in the LTH fetuses.

Conclusion: Despite similar ACTH responses to UCO, the cortisol response was greater in the LTH fetuses than in normoxic controls. LTH appears to result in enhanced adrenal sensitivity to a secondary stressor or altered cortisol metabolism.

Key Words: Cortisol • ACTH • chronic hypoxemia • cord occlusion • fetus

Journal of the Society for Gynecologic Investigation, Vol. 11, No. 3, 131-140 (2004)
DOI: 10.1016/j.jsgi.2003.09.006


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